Pertti Heikman

Urine analysis of 3,4-methylenedioxypyrovalerone in opioid-dependent patients by gas chromatography-mass spectrometry.

A gas chromatography-mass spectrometry (GCMS) procedure was developed for the quantitative analysis of the new designer drug methylenedioxypyrovalerone (MDPV) in urine together with the common stimulants amphetamine, methamphetamine, and methylenedioxymethamphetamine (MDMA). The procedure involved electron ionization (EI) GCMS in the selected ion monitoring (SIM) mode after liquid-liquid extraction with toluene and derivatization with heptafluorobutyric acid anhydride. All MDPV findings were confirmed by positive chemical ionization GCMS in SIM mode. Positive chemical ionization-GCMS allowed the protonated molecule M+H+ m/z 276 to be used as a target ion with 3 abundant fragments as qualifier ions. By electron ionization-GCMS, the limit of quantification (LOQ) for MDPV was 0.02 mg/L; and for amphetamine, methamphetamine, and MDMA, the LOQ was 0.05 mg/L. The method was applied to monitoring urine samples from opioid-dependent patients undergoing opioid substitution treatment. Nine of the 34 urine samples (26%) analyzed were MDPV positive by the GCMS procedure. The positive samples were obtained from 2 female and 7 male patients with a mean age of 31 years. The median (range) MDPV concentration was 0.16 mg/L (0.04-3.9 mg/L) based on the 7 samples for which a numeric value was obtained, whereas the concentration was below the LOQ but above the limit of detection in 2 samples. The method revealed amphetamine in approximately 40% of the cases, and there was no statistical difference between the MDPV-positive and MDPV-negative groups. Urine amphetamine concentrations were on average 10 times higher than those of MDPV. The opioid-dependent patients used MDPV mainly as a substitute for amphetamine, judging from the laboratory findings of this study and the information from our patients.

Right unilateral and bifrontal electroconvulsive therapy in the treatment of depression: a preliminary study.

The short-term outcome of electroconvulsive therapy (ECT) was studied in 24 patients with a current major depressive episode (DSM-IV). Patients were randomized to high dose (400% above the seizure threshold) right unilateral (RUL) ECT, to moderate dose (150% above seizure threshold) RUL ECT, and to low dose (just above seizure threshold) bifrontal (BF) ECT. Primary outcome measures included number of treatments, Hamilton Depression Rating Scale score, and Mini-Mental State Examination score. High dose RUL ECT was associated with a significantly faster response to treatment than low dose BF ECT. Moreover, there was a tendency to a higher response rate with high dose RUL ECT compared with either moderate dose RUL ECT or BF ECT.

Relation between frontal 3-7 Hz MEG activity and the efficacy of ECT in major depression

The efficacy of electroconvulsive therapy (ECT) in major depression has been linked to the accentuation of postconvulsive prefrontal electroencephalography slow-wave activity. We investigated the change in slow-wave activity (0.5–7 Hz) using whole-scalp magnetoencephalographic (MEG) recordings. The 3–7 Hz (theta) activity increased in the right frontal and occipital regions during the course of treatment. After four treatments, the increase of the theta activity in the left frontal cortex correlated with the efficacy of the ECT treatment. Moreover, the change of the ratio of left and right frontal theta activity to occipital theta activity had a positive correlation with the therapeutic effect. These findings suggest that an efficient ECT treatment increases MEG theta activity in the frontal cortex.

Differential response to right unilateral ECT in depressed patients: impact of comorbidity and severity of illness [ISRCTN39974945]

BackgroundRecent electroconvulsive therapy (ECT) efficacy studies of right unilateral (RUL) ECT may not apply to real life clinics with a wide range of patients with major depressive episodes.MethodsThe study included two groups of patients. In addition to a homogeneous group of patients with major depression according to DSM-IV criteria with severity of the major depressive episode > 16 scores on 17-item Hamilton Rating Scale for Depression (HDRS) (Group 1, n = 16), we included a heterogeneous group of patients with less severe major depressive episodes or with a variety of comorbid conditions (Group 2, n = 24). We randomly assigned the patients to an RUL ECT treatment dosed at 5 or 2.5 times seizure threshold with an intent-to-treat design. The outcomes measured blindly were HDRS, number of treatments, and Mini-Mental State Examination (MMSE). The patients were considered to have responded to treatment if the improvement in HDRS score was at least 60% and they had a total score of less than ten.ResultsThe Group 2 patients responded poorer (8% vs. 63%), and had more often simultaneous worsening in their MMSE scores than Group 1 patients. The differences in the outcomes between the two different doses of RUL ECT treatment were not statistically significant.ConclusionsECT effectiveness seems to be lower in real-life heterogeneous patient groups than in homogeneous patient samples used in experimental efficacy trials.

Value of the initial stimulus dose in right unilateral and bifrontal electroconvulsive therapy

BACKGROUND The outcome of electroconvulsive therapy (ECT) is affected by the placement and dose of the stimulus. In general, the ECT dose can be selected either by the dose-titration method (on which the measured seizure threshold level is based), or the method of predetermined dose (e.g. the age-based dosing and the fixed high dose method). METHODS Seizure thresholds were measured in 50 patients with right unilateral (RUL) and in 30 patients with experimental bifrontal (BF) ECT stimulus. The ECT dose (mC) of the age-based dosing was calculated by multiplying the age (years) by 5.0 (age method) or 2.5 (half-age method). The fixed high dose was set to 378 mC. RESULTS The seizure thresholds had only a moderate correlation with the age of the patients. The methods based on the predetermined dose would have led us to give patients with the lowest seizure thresholds in the RUL ECT group very high stimulus doses, up to 12 (age method) or 15 (fixed high dose method) times the individual seizure threshold. In contrast, the RUL ECT patients with the highest seizure thresholds would have received low stimulus doses down to 1.5 times (half-age method) the initial seizure threshold. In the BF ECT group the-age based dose would have been similarly dependent on the initial seizure threshold level. CONCLUSION The use of the dose-titration method is recommended, because it is the only method that allows for the individual selection of ECT stimulus dose relative to the seizure threshold.

Seizures induced by low-dose right unilateral and bifrontal electroconvulsive stimuli.

The duration of electroconvulsive therapy (ECT) seizures of depressive patients has been found to be inversely related to titrated right unilateral (RUL) and bilateral (BL) seizure threshold (ST) levels. This inverse relationship is thought to reflect those neural processes determining seizure duration. The relation between seizure duration and titrated ST level in bifrontal (BF) ECT, which has not been previously studied, is examined here in addition to RUL ECT. We found an inverse relationship in RUL ECT but no relationship in BF ECT. Eighteen percent of RUL patients seized at the first stimulus level versus 40% of BF patients. Compared with previous studies, both our starting dose and the increments between stimuli were greater in BF ECT (50.4 mC) than in RUL ECT (25.2 mC). A relationship between stimulus dose and seizure length may have also been present in BF ECT had similar titration schedules been used for both electrode placements. Future studies using titration schedules with a lower initial dose and finer gradations between stimulus levels are needed to evaluate whether a relationship between stimulus dose and seizure duration exists in BF ECT.

Polydrug abuse among opioid maintenance treatment patients is related to inadequate dose of maintenance treatment medicine

BackgroundPolydrug abuse is a known problem among opioid-dependent patients receiving opioid maintenance treatment (OMT). However, improved laboratory diagnostics is required to reveal polydrug abuse in its current scope. Furthermore, there are few studies focusing on the relationship between polydrug abuse and adequacy of the dose of OMT medicine. This study aimed to evaluate the polydrug abuse among opioid-dependent patients receiving OMT with inadequate (Group IA) and adequate (Group A) doses of OMT medicine as experienced by the patients. Craving for opioids and withdrawal symptoms were evaluated as indicators of the adequacy rating.MethodsThis is a retrospective register-based study of 60 OMT patients on either methadone or sublingual buprenorphine/naloxone medication, whose polydrug abuse was studied from urine samples by means of a comprehensive high-resolution mass spectrometry method.ResultsInadequate doses of the OMT medicines were associated with higher subjective withdrawal scores and craving for opioids. Six groups of abused substances (benzodiazepines, amphetamines, opioids, cannabis, new psychoactive substances, and non-prescribed psychotropic medicines) were found among OMT patients. Group IA patients showed significantly more abuse of benzodiazepines and amphetamines than the Group A patients. All the new psychoactive substances and most of the non-prescribed psychotropic medicines were detected from the Group IA patients. There was no difference in the doses of the OMT medicine between Groups IA and A patients.ConclusionsPolydrug abuse, detected by definitive laboratory methods, was widespread and more common among Group IA than Group A patients, emphasizing the requirement for individual OMT medicine dose adjustment.

Inadequate Dose of Opioid-agonist Medication is Related to Misuse of Benzodiazepines

ObjectivesTo evaluate whether misuse of nonprescribed substances is related to dose-adequacy of opioid-agonist medication (OAM) in opioid substitution treatment. MethodsOpioid-dependent patients undergoing a substitution treatment program of the Helsinki University Central Hospital. Opioid-dependent patients evaluated their dose of OAM (methadone or buprenorphine combined with naloxone) as either too low (group 1) or adequate (group 2). Instead of being limited to the main drug classes detectable by standard immunoassay techniques, this study systematically investigated the incidental use of a very broad spectrum of therapeutic and illicit drugs both from blood and urine samples. ResultsOf the 65 participating patients 21 (32%) completed the study. Their doses and blood concentrations of OAM showed no differences between the 2 groups. The group 1 patients, however, showed more positive laboratory findings for nonprescribed benzodiazepines (7/10 vs. 1/11, P=0.008). Diazepam was present in all positive samples of nonprescribed benzodiazepines, alprazolam in 4, clonazepam in 3, and midazolam in 2 samples. There was no difference in misuse of opiates, amphetamine, cannabis, barbiturates, designer drugs, or psychotropic drugs between groups 1 and 2. ConclusionsThe inadequate dose of OAM in opioid substitution treatment for opioid-dependent patients seems to be related to the misuse of benzodiazepines.